Modeling synchronous growth of bacterial populations in phased cultivation

Abstract

The phasing technique is a method for synchronizing cell populations in a bioreactor. Periodic changes of substrate supply and depletion can provoke a cell cycle phasing of originally stochastic scattered proliferation patterns. Synchronized cell populations characterized by changes in DNA content distribution can be monitored by flow cytometry. Thus, studies of the dynamics of single cells in specific cell cycle phases are facilitated. Here we present an age structured model framework investigating synchronized populations using delay differential equations. Applying the framework not only cell populations synchronously increasing under balanced growth conditions, but also synchronized cultures growing in continuous phasing experiments can be described. A process model developed for describing phased cultures was fitted to growth data obtained from a synchronous cultivation of Cupriavidus necator. Its potential utility is demonstrated by a quantitative process description and by its ability to identify ways in which the grade of synchrony could be improved.